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Preparation and application of novel oral insulin nanoparticles

A kind of use, amino acid technology, applied in the field of new-type specific derivative oral nanoparticles and its preparation, can solve the problems of insulin dependence, pain and inconvenience, easy to cause infection and so on

Inactive Publication Date: 2011-07-13
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, insulin is mostly administered by subcutaneous injection, and long-term insulin injection has many disadvantages: pain and inconvenience, causing psychological pressure for patients; excessive insulin content in local blood, stimulating smooth muscle cell proliferation, and converting glucose into lipid substances on the arterial wall; Local hypertrophy and fat deposition at the injection site due to local precipitation of insulin; dependence on insulin; high cost; easy to cause infection during injection, etc.
[0007] The present invention uses these principles comprehensively to modify histidine and arginine on chitosan and combine them with insulin to prepare nanoparticles to promote its absorption. This study has not been reported yet.

Method used

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  • Preparation and application of novel oral insulin nanoparticles
  • Preparation and application of novel oral insulin nanoparticles
  • Preparation and application of novel oral insulin nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The preparation of embodiment 1N-arginine chitosan

[0028] Get chitosan (Mw 5000, 10000, 100000, 200000, 400000) 1g and add in 100ml 1% acetic acid aqueous solution, stir at room temperature, add a certain amount of arginine (2.92g), NHS (1.94g) and EDC (7.8 g), adjust the pH to 5.5 with acetic acid, react for 48 hours, dialyze with a dialysis bag (MWCO 3500), filter, freeze-dry, and obtain 0.86 g of milky white floc after drying, that is, N-arginine chitosan.

[0029] FTIR: 1620, 1129cm -1 (arginine)

[0030] The degree of deacetylation measured by elemental analysis was 88%, and the degree of substitution of arginine was 11%.

Embodiment 2

[0031] Embodiment 2 Preparation and particle size determination of N-arginine chitosan nanoparticles comprising insulin

[0032] Take 10 mg of N-arginine chitosan, dissolve it in 5 mL of water, and adjust its pH to 5.5 with 0.1 M HCl. Weigh 5mg of insulin, dissolve it in 5mL of 0.01M HCl, and adjust its pH to 8.0 with 0.1M NaOH. Get each 2mL of N-arginine chitosan aqueous solution and insulin solution, mix, stir at room temperature 20min, product solution has blue opalescence, measures nanoparticle particle size with Zetasizer 3000HS particle size analyzer (Malvern Instruments, Malvern, UK) is 120-200nm.

Embodiment 3

[0033] Example 3 N-arginine chitosan promotes the experiment of gastrointestinal absorption of insulin

[0034] After weighing 15 Wistar rats, 70mg·kg -1 The dose weighed STZ (streptozotocin), with 0.7ml citric acid buffer (0.1mol L -1 , pH4.4) dissolved, and immediately intraperitoneally injected into rats. After feeding for 3 days, blood sugar was measured, and the blood sugar value was higher than 16.67mmol·L -1 Rats can continue the experiment. Experimental animals were randomly divided into 3 groups, and fasted for 12 hours before administration, without water. The first group is the insulin control group, which is given intragastric insulin solution (30IU / kg); the second group is the N-arginine chitosan group (the degree of substitution of arginine is 11%), which is given intragastric insulin N-arginine chitosan nanoparticle solution (30IU / kg); the third group is subcutaneous injection group, given subcutaneous injection of insulin solution (2IU / kg). Blood was colle...

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Abstract

The invention relates to preparation and application of oral insulin nanoparticles. The oral insulin nanoparticles mainly comprises a carrier of N-amino acid chitosan and medicinal insulin, are used for treating diabetes and have a better effect of reducing blood sugar.

Description

technical field [0001] The invention relates to a new type of concrete derivative oral nanoparticle and a preparation method thereof, which are mainly used for the treatment of diabetic patients and have the effect of lowering blood sugar. Background technique [0002] Bad eating habits have led to an increase in the number of diabetic patients year by year. For patients with type 1 diabetes and advanced type 2 diabetes, synthetic hypoglycemic drugs are not enough to achieve therapeutic effects, and long-term intake of exogenous insulin is necessary. At present, insulin is mostly administered by subcutaneous injection, and long-term insulin injection has many disadvantages: pain and inconvenience, causing psychological pressure for patients; excessive insulin content in local blood, stimulating smooth muscle cell proliferation, and converting glucose into lipid substances on the arterial wall; Local hypertrophy and fat deposition at the injection site due to local precipitat...

Claims

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Application Information

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IPC IPC(8): C08B37/08A61K38/28A61K47/36A61P3/10
Inventor 吕慧侠莎拉张振海周建平
Owner CHINA PHARM UNIV
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